This invention relates to bismuth containing solid compositions and to a method for their preparation. More particularly, this invention concerns a solid bismuth composition which easily dissolves in water giving a colloidal solution, its preparation and use in pharmaceutical preparations for treatment of peptic ulcer.
A bismuth containing solid composition has been described in British Pat. No. 1,478,742. This known bismuth composition is obtained as a powder by spray drying a colloidal solution which is formed by solving in aqeuous ammonia bismuth citrate, which is a water insoluble compound, and a polyhydric alcohol, usually a sugar e.g. sucrose, sorbitol or mannitol.
The above-mentioned colloidal solution of bismuth citrate, ammonia and polyhydric alcohol has been used for some time and is still in use as the active principle of a therapeutically effective liquid anti-ulcer drug.
The effectiveness of this colloidal bismuth composition was surprising in view of the inactivity of the starting materials, including in particular, solid bismuth citrate in treating peptic ulcers.
Though this drug is very active in healing ulcers, the liquid form has certain disadvantages. The ammoniacal smell is unpleasant for patients taking the liquid; moreover, the liquid is awkward to manage, especially outdoors. Therefore, a solid form of this drug would be very desirable. However, the colloidal solution, being an hydrophobic, inorganic colloid, has been believed to be among the irreversible and irresoluble colloids. Since it is generally known that such systems, i.e., inorganic hydrophobic colloids always loose their colloidal properties during drying, for a long time no attempt was made to prepare a dry form of this drug.
Taking into account all previous experience with this type of hydrophobic colloidal systems, it was very surprising indeed to discover that the powder obtained in the above-described way and disclosed in British Pat. No. 1,478,742 can be redissolved in water without any expedient to provide again a colloidal solution. The colloidal properties of the resultant solution are easily shown by light scattering (Tyndall effect). It is generally known that when a beam of light passes a colloidal solution, a part of the light is scattered sideways.
The resultant solid product has been shown to be as active against ulcers as the original colloidal solution.
It was generally thought by people skilled in the art, that the colloidal solution of bismuth citrate, the spray-drying of which is described in the British patent mentioned above, must contain a compound which is able to stabilize the liquid, to improve its taste and to increase its viscosity considerably. A polyhydric alcohol, preferably a sugar such as sucrose matches all these requirements.
It has been believed that the above-mentioned phenomenon, i.e., ready reconstitution of a colloidal solution from the dried product of an inoganic hydrophobic colloid, previously unknown in the art of hydrophobic colloid chemistry, was the result of the large amount of solved sugar in the colloidal composition. The sugar was thought to prevent the clotting of the colloidal particles into larger insoluble aggregates, presumably due to a protecting layer with which each particle was thought to be coated during spray drying.
In order to stabilize hydrophobic colloids, it is known from prior art to apply compounds, often hydrophilic colloids, which like sugar have a strong interaction with the water structure, which compounds thus increase the viscosity of the colloidal system and lower the speed of flocculation. In fact, polyhydric alcohols, including sugars, are known to have a stabilizing effect on several colloidal systems and dispersions.